The objective of this study is to examine the role of microvascular disease and neuroanatomical changes in the pathophysiology of depression in patients with Non-Insulin Dependent Diabetes Mellitus (NIDDM, Type 2 Diabetes). Vascular factors and structural brain changes have been implicated in the etiology of mood disorders. However, the precise role of microvascular disease, its relationship to anatomical measures and the mechanisms and pathways that lead to depression remain largely unknown. NIDDM is a common metabolic disorder with microvascular compromise in several organs including the Central Nervous System. In addition, the prevalence of major depressive disorder (MDD) in patients with NTDDM is estimated to be approximately 15 percent. This combination renders NTDDM a powerful clinical model to concurrently study the role of structural brain measures and microvascular disease in mood disturbances. We will use magnetic resonance imaging (MRI) to obtain in vivo measures of neuroanatomy. Fundus photography will be used to obtain estimates of retinal microvascular disease, which is conceptualized as a marker of microvascular disease in the brain. We will integrate the biological and behavioral measures and elucidate their collective contributions to the pathophysiology of clinically significant depression.